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SSC- Biology of Cancer > Biological Basis of Cancer Chemotherapy > Flashcards

Biological Basis of Cancer Chemotherapy Flashcards

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1
Q

What are the potential ways that tumours can spread?

A
  • Local
  • Lymphatics
  • Blood
  • Implantation
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2
Q

What is local spread of cancer?

A

Direct involvement of surrounding structures

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3
Q

What cancers spread via the lymphatics?

A
  • Carcinomas
  • Melanomas
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4
Q

What cancers spread via the blood?

A
  • Sarcomas
  • Later stage carcinomas
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5
Q

What happens in implantation spread of cancer?

A

There is mechanical spread of detatched clumps of tumour cells to the peritoneum, ureters, or CSF

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6
Q

What are the treatment options for cancer?

A
  • Surgery
  • Radiotherapy
  • Chemotherapy
  • Hormones
  • Biologically targetted therapy
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7
Q

In what ways can chemotherapy be used in treating cancer?

A
  • Radical primary treatment
  • Adjuvant therapy
  • Neoadjuvant therapy
  • Palliative care in advanced disease
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8
Q

Where is chemotherapy used as a radical primary treatment?

A

In haemotological malignancies, such as lymphomas and leukaemias

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9
Q

What is the definition of adjuvant chemotherapy?

A

Post-operative treatment in a patient at high risk of microscopic metastases after the removal of the primary tumour

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10
Q

What is neoadjuvant chemotherapy?

A

Primary treatment of patients with clinically localised tumour - use chemotherapy upfront to improve the outcome of the primary therapy

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11
Q

What are the advantages of neoadjuvant chemotherapy?

A
  • Can assess the biological responsiveness of the tumour
  • May allow for conservation surgery
  • May achieve pCR (pathological complete response
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12
Q

What determines the rate of tumour growth?

A
  • Growth fraction
  • Duration of cell cycle
  • Rate of cell loss
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13
Q

What does topoisomerase 1 do?

A

It causes transient single strand cleavage, relaxes the strand, and then sticks it back together

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14
Q

How does topoisomerase 1 inhibition work?

A

You get binding to the TOPO 1-DNA complex, without affecting the cleavage region. This means that the enzyme cannot rejoin the DNA, resulting in a double stranded break and therefore cell apoptosis

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15
Q

What is the advantage of a unique tumour-activated agent?

A

It wouldn’t affect normal tissue, and so minimises side effects

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16
Q

Give an example of a tumour activated chemotherapy agent?

A

Xeloda

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17
Q

What is the mechanism of action of xeloda?

A
  1. It is absorbed in the intestine
  2. It is converted to 5’-DFCR CyD and then 5’-DFUR
  3. 5’-DFCR CyD and 5’-DFUR are transported into the tumour tissue, where they are converted to 5-FU
  4. 5-FU blocks DNA replication
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18
Q

What happens to spindle microtubules once chromosomes are aligned at the metaphase plate?

A

They depolymerise, moving sister chromatids towards opposite poles

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19
Q

How do micro-tubule binding agents affect microtubule dynamics?

A
  • Inhibit polymerisation
  • Stimulate polymerisation and prevent depolymerisation
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20
Q

What does it need to be ensured if combination therapy is to improve activity?

A
  • Drugs have a different mechanism of action
  • Drugs have different mechanisms of resistance
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21
Q

What needs to be ensured if combination therapy is to be safe?

A

They have compatible side effects

22
Q

What is P-glycoprotein?

A

An ATP-powered efflux pump

23
Q

What does P-glycoprotein do?

A

Pumps cytotoxic agents out of the cells against the concentration gradient

24
Q

What repair pathway is employed in single-stand breaks?

A

Base excision repair

25
Q

What enzyme is used in base excision repair?

A

PARP

26
Q

What repair pathway is employed in double stranded DNA breaks?

A

Recombinational repair

27
Q

What enzymes are used in recombinational repair?

A
  • ATM in homologous recombination repair
  • DNA-PK in non-homologous end joining
28
Q

What repair pathway is employed when bulky adducts are added to DNA?

A

Nucleotide-excision repair

29
Q

What enzymes are used in nucleotide-excision repair?

A
  • XP
  • Polymerases
30
Q

What repair pathway is employed with insertions and deletions to DNA?

A
  • MSH2
  • MLH1
31
Q

What repair pathway is employed with O6-alkylguanine DNA damage?

A

Direct reversal

32
Q

What enzyme is involved in direct reversal of O6-alkylguanine mutations?

A

AGT

33
Q

Give the process of repair of single strand DNA breaks by PARP-1

A
  1. PARP binds directly to single strand breaks
  2. Once bound to damaged DNA, PARP modifies itself producing large branches chains or PAR
  3. PAR recruits repair enzymes, which fix the break
  4. PAR chains are degraded via PARG
34
Q

What effect does inhibiting PARP-1 have on DNA?

A

It increases double stranded DNA breaks, as it prevents recruitment of repair factors to repair SSB, which then progress to DSB after S-phase of DNA replication

35
Q

Give an example of a homologous recombination repair deficient cell

A

Cells with BRCA 1 or 2 mutations

36
Q

How does olaparib work in BRCA-deficient cancer cells?

A

It causes double strand breaks, which can be repaired effectively by HR pathways in normal cells, allowing them to survive, but kills cancer cells as they don’t have the pathway to repair

37
Q

Give two examples of hormones that can be carcinogenic

A
  • Oestrogen in breast cancer
  • Testosterone in prostate cancer
38
Q

What is important when considering carcinogenic hormones?

A

Prolonged exposure, e.g. in the case of breast cancer, should consider age of menarche, age of first pregnancy etc

39
Q

What are the categories of endocrine therapies for breast cancer?

A
  • Anti-oestrogens
  • Aromatase inhibitors
  • Progestogens
  • LHRH agonists
40
Q

Give an example of an anti-oestrogen breat cancer therapy

A

Tamoxifen

41
Q

Give 5 examples of aromatase inhibitors

A
  • Anastrazole
  • Letrozole
  • Exemestane
  • Vorozole
  • Formestane
42
Q

Where do aromatase inhibitors have a particular use?

A

When women are post menopausal

43
Q

Why do aromatase inhibitors have a particular role when women are post-menopausal?

A

Because they are reliant on the aromatase enzyme to produce any oestrogen

Doesn’t work in pre-menopausal women, as they are producing their own ovarian oestrogen

44
Q

Give an example of a progtesterone therapy for breast cancer

A

Megestrol

45
Q

Give an example of a LHRH agonist

A

Goserelin

46
Q

What are the categories of endocrine therapies for prostate cancer?

A

LHRH agonists

Anti-androgens

Oestrogen

Castration

47
Q

Give 3 examples of anti-androgens

A
  • Cytoproterone acetate
  • Flutamide
  • Bicalutamide
48
Q

Give an example of an oestrogen therapy for prostate cancer

A

Stilboestrol

49
Q

How does giving oestrogen help in prostate cancer?

A

It compensates for the testosterone drive for prostate cancer

50
Q

Give an example of a novel endocrine agent used in the treatment of prostate cancer

A

Abiraterone

51
Q

What is the mechanism of action of abiraterone?

A

It inhibits the crucial CYP17A1 enzyme, which is needed for the conversion of pregnenolone and progesterone to testosterone

SSC- Biology of Cancer (11 decks)

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